Warning(s)

Suicidality

Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.101103104a Tranylcypromine is not approved for use in pediatric patients.101a (See Pediatric Use under Cautions.)

In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.101103104a

Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.101103104105a

Appropriately monitor and closely observe all patients who are started on tranylcypromine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.101103104105a (See Worsening of Depression and Suicidality Risk and Pediatric Use under Cautions.)

Uses for Tranylcypromine Sulfate

Major Depressive Disorder

Efficacy in major depressive disorder with melancholia (endogenous features) not established.101ad

Slideshow: Depression, the Risk of Suicide, and Treatment Options

MAO inhibitors appear particularly effective in treatment of major depressive disorder with atypical features, although other antidepressants (e.g., SSRIs) may initially be used because of their more favorable adverse effect profile.102ef

Because of potential for serious adverse effects and necessity of dietary restrictions, MAO inhibitors (e.g., phenelzine, tranylcypromine) generally are not used as initial therapy for major depressive disorder, but are reserved for carefully selected patients who can be closely supervised and who have depression refractory to other antidepressants (e.g., SSRIs, SNRIs, TCAs) or in whom other therapies are contraindicated.101102adef

Tranylcypromine Sulfate Dosage and Administration

General

Allow at least 1–2 weeks to elapse between discontinuance of therapy with another MAO inhibitor, dibenzazepine derivative (including carbamazepine and cyclobenzaprine), or TCA and initiation of tranylcypromine and vice versa.101aepq

Allow at least 2 weeks to elapse between discontinuance of tranylcypromine and initiation of bupropion.101ae

Allow at least 2 weeks to elapse between discontinuance of an SSRI and initiation of tranylcypromine and vice versa.101a Also allow at least 5 weeks to elapse when switching from fluoxetine.101a

Allow at least 5 or 7 days to elapse between discontinuance of duloxetine or venlafaxine, respectively, and initiation of tranylcypromine and at least 2 weeks between discontinuance of tranylcypromine and initiation of duloxetine or venlafaxine.cn

Allow at least 10 days to elapse between discontinuance of tranylcypromine and initiation of buspirone.101a

Allow at least 2–3 weeks to elapse between discontinuance of tranylcypromine and meperidine administration.101ar

Patients receiving tranylcypromine should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.101103104105a (See Worsening of Depression and Suicidality Risk under Cautions.)

Administration

Oral Administration

Administer orally in divided doses.101a Administration earlier in the day (e.g., twice daily in the morning and afternoon) may reduce incidence of insomnia.d101a

Dosage

Available as tranylcypromine sulfate; dosage expressed in terms of tranylcypromine.101ad

Individualize dosage carefully according to individual requirements and tolerance.100101ad

Adults

Major Depressive Disorder

Oral

Usual dosage: 30 mg daily, usually given in 2 divided doses in the morning and afternoon.101ad If no signs of therapeutic response appear after a reasonable period (up to 2–3 weeks), may increase dosage in increments of 10 mg daily at 1- to 3-week intervals until optimum therapeutic response or dosage of 60 mg daily is reached.101ad

Dosages >30 mg daily may be associated with an increased frequency and severity of adverse effects.100101ad (See Orthostatic Hypotension under Cautions.) May reduce dosage to lower maintenance dosage once adequate response achieved.d

Warnings/Precautions

Warnings

Shares the toxic potentials of other MAO inhibitors; observe the usual precautions and contraindications associated with therapy with these drugs.de Should be used only by clinicians who are completely familiar with proper use, potential adverse effects, and associated precautions and contraindications of MAO inhibitors.101ade Fully advise patients about risks, especially hypertensive crisis and suicidal thinking and behavior (suicidality), associated with MAO inhibitor therapy.101ade

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.101103104105106a However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.101103104105a

Appropriately monitor and closely observe patients receiving tranylcypromine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.101103104105a (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.101104105a Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.103104105

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.101104a

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.101104a

Bipolar Disorder

May unmask bipolar disorder.101104a (See Activation of Mania or Hypomania under Cautions.) Tranylcypromine is not approved for use in treating bipolar depression.101a

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.101104a

Hypertensive Crises

Hypertensive crises, sometimes fatal, are one of the most serious adverse effects associated with MAO inhibitors, including tranylcypromine.101102ae Although spontaneous cases reported, most cases occurred following ingestion of foods or beverages containing large amounts of tyramine (i.e., cheese reaction) or when MAO inhibitors were used concomitantly with certain prescription or OTC drugs.101ae (See Specific Drugs and Foods under Interactions and see also Advice to Patients.)

Closely monitor BP in all patients to detect evidence of pressor response; however, full reliance should not be placed on BP determinations alone.101ae Frequently observe patient’s clinical status, particularly for signs and symptoms of hypertension.101ae

If a hypertensive crisis or prodromal signs of hypertensive crisis occur, discontinue MAO inhibitor therapy and immediately institute appropriate therapy to lower BP.101ae Phentolamine considered hypotensive drug of choice for treating MAO inhibitor-induced hypertensive crisis.101102ae Manage fever by external cooling.101ae Other symptomatic and supportive measures may be necessary in some patients; however, avoid administration of parenteral reserpine.101ae (See Contraindications under Cautions and see Specific Drugs and Foods under Interactions.)

At dosages >30 mg daily, postural hypotension is an important adverse effect and may cause syncope.101a In patients who show some hypotensive response during initiation of MAO inhibitor therapy, increase dosage more gradually.101ae May relieve postural hypotension by having patient lie down until BP returns to normal.101ae

Myelography

Avoid concurrent use of drugs that lower seizure threshold, including MAO inhibitors, and metrizamide (no longer commercially available in US).101ae Discontinue tranylcypromine ≥48 hours prior to myelography; do not resume therapy for ≥24–48 hours post-procedure.101ae (See Specific Drugs and Foods under Interactions.)

Cardiovascular Effects

MAO inhibitors may suppress anginal pain that would otherwise serve as a warning sign of myocardial ischemia; warn patients with angina pectoris or coronary artery disease against overexertion.101ae

Specific Populations

Pregnancy

Lactation

Pediatric Use

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).101104a However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.106 No suicides occurred in these pediatric trials.101104106a

Carefully consider these findings when assessing potential benefits and risks of tranylcypromine in a child or adolescent for any clinical use.101103104105106a (See Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

Clinical experience with MAO inhibitors has not identified any differences in responses between geriatric and younger adults.e

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.101103104a (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Possible increased morbidity during or following episodes of hypertension or malignant hyperthermia; geriatric patients have less compensatory reserve to cope with any serious adverse reaction.101ae

Allow at least 5 or 7 days to elapse between discontinuance of duloxetine or venlafaxine, respectively, and initiation of tranylcypromine and at least 2 weeks between discontinuance of tranylcypromine and initiation of duloxetine or venlafaxinecn

Delirium reported in humans;i severe toxicity, including seizures and death, reported during concurrent administration in animals in 1 study but no adverse interactions reported in other animal studies101a

Onset

Pharmacologic effects of MAO inhibitors are cumulative; onset of pharmacologic action of tranylcypromine is more rapid than that of hydrazine-derivative MAO inhibitors (e.g., phenelzine).de Antidepressant effect usually evident within 2 days–3 weeks.101ae

Duration

Inhibition of MAO may persist up to 10 days following drug discontinuance.101a

Distribution

Extent

Elimination

Metabolism

Elimination Route

Excretion is rapid, occurring within 24 hours after drug discontinuance; however, urinary tryptamine concentrations, which are used to measure MAO activity, return to normal within 72–120 hours.100101adl

Half-life

Stability

Storage

Oral

Tablets

Well closed, light-resistant containers at 20–25°C (may be exposed to 15–30°C).101ad

Actions

Principal pharmacologic effects of tranylcypromine are similar to those of other nonselective MAO inhibitors (e.g., phenelzine).de

Tranylcypromine binds reversibly to the MAO enzyme while phenelzine binds irreversibly to the enzyme.e

Precise mechanism of antidepressant action is unknown but may involve increases in free serotonin and norepinephrine and/or alterations in other amine concentrations within the CNS.101aef100

Advice to Patients

Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.101103104105a FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.101103104105a

Importance of patients informing their clinicians and dentist that they are taking tranylcypromine.101a

Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.101a

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal or nutritional supplements, as well as any concomitant illnesses.101a

Importance of informing patients of other important precautionary information.101a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Tranylcypromine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

10 mg (of tranylcypromine)

Parnate

GlaxoSmithKline

Tranylcypromine Sulfate

Par

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.